Three polymorphisms of renin-angiotensin system and preeclampsia risk

PurposeSome data suggest an association between the single nucleotide polymorphisms AGT T704C, ACE I/D, and AT1R A1166C and preeclampsia, but overall, the data are conflicting; the aim of our study was to discover a more stable and reliable association between these polymorphisms and PE risk.MethodsA comprehensive literature search for this meta-analysis was conducted. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated to evaluate the strength, and heterogeneity test was conducted. Trial sequential analysis was also performed.ResultsA total of forty studies were finally included in our meta-analysis. The AGT T704C polymorphism was associated with PE risk in three genetic models (dominant OR = 1.33, 95%CI = 1.12–1.59; heterozygote OR = 1.26, 95%CI = 1.05–1.52; homozygote OR = 1.44, 95%CI = 1.14–1.83). No heterogeneity was observed in the three genetic models for the ACE I/D polymorphism. For subgroup analysis by geography, no significant association was detected. Significant associations were observed in mixed race, early-onset, late-onset, and more than 200 subgroups for the AT1R A1166C polymorphism; however, only one study was analyzed in these subgroups.ConclusionsOur results indicated the AGT T704C and ACE I/D polymorphisms were associated with an increased risk of PE. Increased risks were also observed for the two polymorphisms in subgroups including Asians, Europeans, Caucasoid, and Mongoloid. Moreover, an increased PE risk with the ACE I/D polymorphism in the severe PE population was also detected. Regarding the AT1R A1166C polymorphism, weak associations were observed, but further studies are required.Electronic supplementary materialThe online version of this article (10.1007/s10815-020-01971-8) contains supplementary material, which is available to authorized users.     

Maternal serum and fetal cord-blood ischemia-modified albumin concentrations in normal pregnancy and preeclampsia: a systematic review and meta-analysis

Background/aims: A meta-analysis of maternal serum ischemia-modified albumin (IMA) and fetal cord-blood IMA concentrations in normal pregnancy (NP) compared to non-pregnant healthy controls (HC) and in preeclampsia (PE) compared with normal pregnant controls were studied.

Methods: All major databases were searched for eligible studies. We included eight studies comparing serum IMA between NP and HC, 14 studies comparing serum IMA between PE and NP and five studies comparing cord-blood IMA between PE and NP groups. Meta-analyses on these included studies were performed using Review Manager 5.3. Pooled-overall effect size as standardized mean difference (SMD), publication bias, subgroup, and sensitivity analysis data were generated.

Results: Random-effects meta-analysis indicated a significant increase in serum IMA in the NP group (SMD?=?0.98, p?=?.01) and the PE group (SMD?=?0.94, p?p?Conclusions: This meta-analysis, the first of its kind showed that the increased serum IMA concentrations were indicative of increased oxidative stress in NP and PE. Measurement of maternal serum IMA and fetal cord-blood IMA concentrations were useful as simple, novel, and inexpensive markers of oxidative stress (OS) status in PE patients. Future large-scale studies are needed to explore IMA in relationship to the disease severity in PE.     

Association between bile salt export pump polymorphisms and intrahepatic cholestasis of pregnancy susceptibility: a meta-analysis of case-control studies

The purpose of this meta-analysis was to investigate the relationship between bile salt export pump (BSEP) polymorphisms and intrahepatic cholestasis of pregnancy (ICP) susceptibility. Retrieved studies from Pubmed, EMBASE, Web of Science, Cochrane Library and CBM databases about BSEP polymorphisms and ICP susceptibility were included. Odds ratio (OR) and 95% confidence interval (CI) and publication bias were calculated. Ten related case-control studies on BSEP polymorphisms and ICP susceptibility were included. The pooled results showed a significant association between BSEP rs2287622 polymorphism and ICP risk in Asian population (OR >1, p?<?.01 for A vs. a and AA vs. Aa/aa) and general population (OR >1, p?<?.05 for A vs. a, Aa vs. aa, AA/Aa vs. aa), and a borderline statistical significance was found between BSEP rs473351 polymorphism and ICP susceptibility (OR?=?1.66, p?<?.05), and no statistical significance was found in D482G or rs853782 polymorphisms and ICP risk (all p?>?.05). Additionally, no publication bias was found in these studies (all p?>?.05). Our current meta-analysis indicated that BSEP rs2287622 polymorphism could increase the susceptibility of ICP in Asians and in general populations, while rs473351, D482G, and rs853782 polymorphisms were not obviously associated with ICP risk, but it needs further larger study with ethnicity and various etiologies.     

Is maternal smoking during pregnancy associated with an increased risk of congenital heart defects among offspring? A systematic review and meta-analysis of observational studies

Objective: To investigate the association between maternal smoking during pregnancy and risk of congenital heart defects (CHDs) among offspring.

Methods: PubMed, EMBASE, and Web of Science were searched for eligible studies. The outcomes of interest included risk of any CHD and nine subtypes. We summarized study characteristics and used a random-effects model in meta-analysis, and a two-stage dose–response model was utilized to assess the association between smoking consumption and risk. Statistical heterogeneity was assessed by a chi-squared test of the Cochrane Q statistic and I-squared value. Publication bias was assessed by funnel plots and Egger’s test, and trim and fill method was utilized when publication bias existed.

Results: Forty-three observational epidemiologic studies were included. The pooled risk ratio (RR) of any CHD was 1.11 (95% CI: 1.04, 1.18), but it exhibited substantial statistical heterogeneity (p?I^2?=^?69.0%). In sensitivity analysis, we observed significant associations for atrial septal defect (ASD) and marginally significant associations for septal defects (SPD). The two-stage dose–response analysis showed evidence to support that higher levels of tobacco smoke was associated with an increased risk of septal defects, particularly for ASD and VSD (ventricular septal defect).

Conclusion: Our study presents evidence to support the cardiovascular teratogenic effect of maternal smoking during pregnancy, and their offspring may suffer from approximately a 10% relative increase in the risk of CHDs on average.     

The association between maternal smoking and placenta abruption: a meta-analysis

Background: Several epidemiological studies have determined that maternal smoking can increase the risk of placenta abruption. To date, only a meta-analysis has been performed for assessing the relationship between smoking and placenta abruption. This meta-analysis was conducted to estimate the association between smoking and the risk of placenta abruption.

Methods: A literature search was conducted in major databases such as PubMed, Web of Science, and Scopus from the earliest possible year to April 2016. The heterogeneity across studies was explored by Q-test and I² statistic. The publication bias was assessed using Begg’s and Egger’s tests. The results were reported using odds ratio (OR) estimate with its 95% confidence intervals (CI) using a random effects model.

Results: The literature search yielded 1167 publications until April 2016 with 4?309?610 participants. Based on OR estimates obtained from case–control and cohort studies, there was a significant association between smoking and placenta abruption (1.80; 95% CI: 1.75, 1.85). Based on the results of cohort studies, smoking and placenta abruption had a significant association (relative risk ratio: 1.65; 95% CI: 1.51, 1.80).

Conclusions: Based on reports in epidemiological studies, we showed that smoking is a risk factor for placenta abruption.     

Association between COMT Val158Met polymorphism and preeclampsia in the Chinese Han population

Objective: Previous studies have been indicated that catechol-O-methyltransferase gene (COMT) might play a significant role in the development of preeclampsia (PE). Our study aims to investigate the association between polymorphism in COMT with the susceptibility to PE in Chinese Han women. Method: A total of 1028 PE patients and 1399 normal pregnant women were enrolled. We detected the genotyping of COMT Val158Met loci by the TaqMan allelic discrimination real-time PCR . Results: No significant difference in the genotypic and allelic distribution was found between the two groups (genotype: X² = 0.583, p = 0.747; allele:X² = 0.526, p = 0.468). Conclusion: The COMT Val158Met polymorphism might not be associated with PE in Chinese women.     

A diagnostic test accuracy meta-analysis of maternal serum ischemia-modified albumin for detection of preeclampsia

Background/aims: Ischemia-modified albumin (IMA) has been widely accepted as a serological biomarker. IMA has been proposed as a simple and novel marker of oxidative stress in preeclampsia (PE). This systematic review and diagnostic test accuracy meta-analysis aims to evaluate the diagnostic accuracy of this novel serological biomarker, IMA to detect PE.

Methods: A systematic search of major databases was performed to identify all published diagnostic accuracy studies on IMA. Risk of bias and applicability concerns were assessed for included studies. Summary estimates; the pooled sensitivity, specificity, and the diagnostic odds ratio (DOR) of IMA for the diagnosis of PE were computed using random-effects models. The overall test performance was summarized using summary receiver operating characteristic (SROC) curve analysis.

Results: Six articles were included in this meta-analysis. The overall estimates of IMA in detecting PE were pooled sensitivity; 0.80 (95%CI 0.73–0.86), pooled specificity; 0.76 (95%CI 0.70–0.81), DOR; 14.32 (95%CI 5.06–40.57), and area under curve (AUC); 0.860. There was no between-study heterogeneity due to threshold effect.

Conclusions: This meta-analysis showed IMA could be useful as a biomarker for PE with good accuracy (AUC?=?0.860). However, further research is needed for re-evaluation and clinical validation of fairly promising results of this meta-analysis.     

The significance of −786T > C polymorphism of endothelial NO synthase (eNOS) gene in severe preeclampsia

Objective.?Preeclampsia (PE) is believed to be induced by endothelial cell dysfunction in placenta. Highly polymorphic endothelial nitric oxide synthase (eNOS) activity belongs to the factors significantly influencing vaso-motor tone in placenta and PE susceptibility. The aim of this study was to evaluate prevalence of ?786T/C polymorphism of eNOS gene in the groups of women with mild and severe PE.

Study design.?The study was performed in the group of 218 preeclamptic (including 136 with severe PE) and of 400 normotensive healthy women delivered normally after a healthy gestation. The eNOS ?786T/C polymorphism was determined using PCR/RFLP assay. Additionally, detailed correlation between eNOS genotypes and clinical/laboratory data in the PE group has been analyzed.

Results.?The higher frequency of mutated homozygous CC genotypes (17.4% vs. 11.5% in controls, OR 1.62, n.s.) and of C alleles (allelic frequency 44.1 vs. 36.6%; OR 1.36, p = 0.012) in the group of PE has been determined. Furthermore, in the group of severe PE the overrepresentation of mutated CC genotypes (23.5% vs. 11.5%, OR 2.37, p = 0.0014) and mutated C alleles (47.8 vs. 36.6%, OR 1.58, p = 0.0016) has been found.

Conclusions.?The presence of mutated homozygous CC genotype and C allele of ?786T/C polymorphism of eNOS gene influences the higher susceptibility to develop severe PE development.     

Association between maternal HBsAg carrier status and neonatal adverse outcomes: meta-analysis

Objective: We conducted a meta-analysis to evaluate whether maternal hepatitis B virus (HBV) carrier status increases the risk of neonatal complications.

Methods: Publications addressing the association between maternal HBV carrier status and neonatal outcomes were selected from the PubMed, EMBASE, Web of Science, Cochrane Library and China National Knowledge Infrastructure. Publication bias and heterogeneity across studies were evaluated and summary odds ratios, weighted mean difference or standardized mean difference and 95% confidence intervals were calculated and compared between groups.

Results: Eighteen studies and 7600 pregnant HBV carriers were selected for analyses. A statistically association with maternal HBV carrier status was demonstrated for premature birth and asphyxia, with no difference found among perinatal mortality, gestational age, small for gestational age, large for gestational age, birth weight, low birth weight, macrosomia, Apgar sore at 1?min, jaundice and congenital anomaly. Heterogeneity across studies was found, and no publication bias was detected.

Conclusion: Our analysis suggests that maternal hepatitis B carrier status is significantly associated with premature birth and asphyxia. Large-scale prospective studies are still warranted.     

Maternal anti-protein Z antibodies in pregnancies complicated by pre-eclampsia,SGA and fetal death

Objective.?Low maternal plasma protein Z (PZ) concentrations were reported in patients with pre-eclampsia (PE), a small for gestational age (SGA) neonate, and a fetal demise (FD). Anti-protein Z antibodies (APZ-AB) have been proposed as a possible underlying mechanism leading to low plasma PZ concentrations. The objective of this study was to determine the maternal plasma concentration of APZ-AB in women with a normal pregnancy, and patients with PE, an SGA neonate or a FD.

Study design.?A cross-sectional study included women in the following groups: (1) non-pregnant women (n = 45); and pregnant women with: (2) normal pregnancies (n = 70); (3) PE (n = 123); (4) SGA neonates (n = 51); and (5) a FD (n = 51). Plasma concentrations of anti-protein Z IgM and IgG antibodies were measured by ELISA. Elevated APZ-AB was defined as >75th, 90th and 95th percentile of the normal pregnancy group. Non-parametric statistics were used for analyses.

Results.?(1) Patients with an SGA neonate had a higher median maternal plasma IgG APZ-AB concentration than women with normal pregnancies (p < 0.001), and patients with PE (p < 0.001) or with a FD (p = 0.001). (2) The proportion of patients with a maternal plasma IgM APZ-AB concentration >90th percentile was higher in the SGA group than in the PE group (p = 0.01). (3) Patients with PE maternal plasma IgM APZ-AB concentration >90th percentile had a higher rate of villous thrombosis (p = 0.03) and persistent muscularisation of basal plate arteries (p = 0.01) than those with IgM APZ-AB concentration <90th percentile; and (5) Patients with FD and maternal plasma IgM APZ-AB concentration >90th percentile had a higher rate of umbilical phlebitis and arteritis than those with IgM APZ-AB concentration <90th percentile (p = 0.003).

Conclusions.?(1) Patients with SGA neonates have a higher median plasma concentration of IgG APZ-AB than normal pregnant women, or patients with PE or FD; and (2) maternal plasma IgM APZ-AB concentration >90th percentile was associated with vascular placental lesions in patients with PE, but not in those with an SGA neonate, suggesting that in a subset of patients, these antibodies can be associated with abnormal placentation and pregnancy complications.     

The association between body mass index and preeclampsia: a meta-analysis

Background: Several observational studies have reported a positive association between elevated body mass index (BMI) and preeclampsia, but no meta-analysis has been conducted yet. This meta-analysis was conducted to estimate the overall association between overweight or obesity and preeclampsia.

Methods: Major electronic databases, including PubMed, Web of Science, and Scopus were searched until August 2015. The reference lists of included studies were screened as well. Epidemiological studies addressing the association between BMI and preeclampsia were enrolled. The heterogeneity across studies was explored by Q-test and I² statistic. The possibility of publication bias was assessed using Begg's and Egger's tests. The results were reported using odds ratio (OR) estimate with its 95% confidence intervals (CI) using a random-effects model.

Results: We identified a total of 1298 references and included 23 studies with 1 387 599 participants. Preeclampsia was associated with overweight (OR?=?1.73; 95% CI: 1.59, 1.87; 21 studies; I^2?=^?62.3%) and obesity (OR?=?3.15; 95% CI: 2.96, 3.35; 22 studies; I^2?=^?36.0%). There was no evidence of publication bias.

Conclusions: There is sufficient evidence that excess body mass index is significantly associated with an increased risk of preeclampsia. Therefore, overweight and obesity can be considered as a predictor of preeclampsia.     

Maternal education and breastfeeding practices in China: A systematic review and meta-analysis

Objectiveto examine the association between maternal education and breastfeeding prevalence in China.Methodsa systematic review and meta-analysis was conducted based on the literature of observational studies retrieved from electronic databases of CNKI, Medline, Embase, CINHAL, ProQuest and Science Direct. Maternal education was recoded into two binary categorical variables using different cut-off points. Both fixed and random effect models were used to estimate the pooled association between maternal education and breastfeeding prevalence in China. Visual inspection of Galbraith plot for heterogeneity detection, sensitivity analysis and publication bias test were performed.Findingsa total of 31 studies were included in the systematic review, and 15 and 26 studies were suitable for meta-analysis in terms of two different cutoff points of maternal education respectively. In the group using 6-year education cut-off (Group 1), the odds of breastfeeding was 10% (pooled OR=0.90, 95% CI: 0.83, 0.97) lower in mothers who had been educated for 'more than 6 years' compared to mothers with '6 years or less' education.In the group using 12-year education cut-off (Group 2), the odds of breastfeeding was 9% (pooled OR=0.91, 95% CI: 0.86, 0.96) lower in mothers who had 'more than 12 years' education compared to mothers who attained '12 years or less' education. There was substantial heterogeneity across the studies in both groups. Through meta-regression analysis, sample size of studies was detected contributing to the heterogeneity in Group 1; however none of study level factors were found to be a source of heterogeneity in Group 2.Conclusionin the Chinese culture and employment environment, mothers who have attained a higher level of education are less likely to breastfeed their babies compared to mothers with lower education levels.     

Erectile Dysfunction and Premature Ejaculation in Homosexual and Heterosexual Men: A Systematic Review and Meta-Analysis of Comparative Studies

Introduction

Comparative studies on differences in sexual function outcomes between homosexual and heterosexual men are sparse and inconclusive.

Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for preeclampsia: a meta-analysis

Objectives

MTHFR C677T and A1298C have been associated with the risk of preeclampsia (PE), but with conflicting results. We performed this meta-analysis to derive a more precise estimation of the association between MTHFR polymorphisms and PE.

Study design

An electronic search of PubMed and Chinese Biomedicine database was conducted to select studies for meta-analysis. 54 case controlled studies containing MTHFR C677T and A1298C gene polymorphisms were chosen, and odds ratio (OR) with confidence interval (CI) was used to assess the strength of this association.

Result

These studies evaluated 7398 cases and 11230 controls for MTHFR C677T. The overall results suggested that MTHFR C677T was associated with the risk of PE. (T vs. C: OR = 1.157, 95 % CI: 1.057-1.266, p=0.002; TT+CT vs. CC: OR=1.165, 95 % CI : 1.049-1.293, P = 0.004; TT vs. CT + CC: OR = 1.371, 95 % CI: 1.153-1.63, p < 0.001). We also evaluated 1103 cases and 988 controls for MTHFR A1298C but could not demonstrate an increased risk of PE for this polymorphism (p=0.667). A symmetric funnel plot, the Egger’s test (p = 0.819) suggested a lack of publication bias.

Conclusion

This meta-analysis supports the idea that MTHFR C677T genotype is associated with increased risk for PE, especially in the case of Asians and Caucasians.     

Preeclampsia and maternal risk of breast cancer: a meta-analysis of cohort studies

Background: Pregnancy-related hypertensive disorders, including preeclampsia (PE) and pregnancy-induced hypertension (PIH), may influence the maternal risk of breast cancer. However, results of the cohort studies were inconsistent.

Methods: An updated meta-analysis of cohort studies was performed to evaluate the association between PE, PIH and maternal breast cancer incidence. Relevant studies were identified via searching of PubMed and Embase databases. A random effect model was applied to synthesize the results. Stratified analyses were performed to evaluate the potential influence of parity, gender of offspring, and study design on the association between PE and maternal breast cancer incidence.

Results: Ten cohort studies with 2,417,899 pregnant women were included. Maternal risk of breast cancer was not significantly affected by PE (risk ration [RR]?=?0.93, 95% confidence interval [CI]: 0.82–1.06, p?=?.27), or PIH (RR?=?0.95, 95% CI: 0.81–1.12, p?=?.54). Interestingly, PE was associated with significantly lowered maternal incidence of breast cancer in women who give birth to male offspring (RR?=?0.79, p?p?Conclusions: Current evidence did not support a conclusive association between PE, PIH and the maternal risk of breast cancer. Gender of the offspring may influence the association between PE and maternal breast cancer incidence.     

Endothelial Nitric Oxide Synthase Polymorphisms and Erectile Dysfunction: A Meta-Analysis

Introduction and AimsErectile dysfunction (ED) is a frequent disorder in men and has a serious impact on the quality of the patient's life. Recent studies have examined the relationship between endothelial nitric oxide synthase (eNOS) polymorphisms and ED. However, the results remain inconclusive. The present study aimed to offer an actual view of estimating the correlation between eNOS polymorphisms and ED.MethodsWe performed a meta-analysis to estimate the association between eNOS polymorphisms and ED risk. Databases employed for data mining until December 1, 2014 included PubMed, Web of Science, and the Chinese National Knowledge Infrastructure. Two study investigators independently conducted a literature search and data extraction. Odds ratios (ORs) with 95% confidence intervals for the risk were calculated by using a random effects model or fixed effects model.ResultsA total of 20 studies in 13 publications were included in the meta-analysis. In the overall comparison, the eNOS G984T polymorphism was associated with an increased ED risk in allele contrast, dominant, heterozygote, and homozygote models (allele contrast: OR = 1.514, 95% confidence interval [CI]: 1.019–2.248). For 4 VNTR polymorphisms, the overall analysis showed a significant association between homozygote comparison and recessive genetic model (homozygote comparison: OR = 1.917, CI: 1.073–3.424). The eNOS T786C polymorphism increased ED risk in allele contrast, homozygote, and recessive models (allele contrast: OR = 1.588, CI: 1.316–1.915). Significant heterogeneity was mainly observed in studies on the G894T polymorphism. No publication bias was detected in all of the variants.ConclusionThe eNOS polymorphisms G894T, 4 VNTR, and T786C were associated with an increased risk for ED. However, these results are still preliminary. Further studies based on different confounders and using a large population size should be conducted to generate more accurate and reliable conclusions. Liu C, Lu K, Tao T, Zhang L, Zhang X, Jiang L, Huang Y, Guan H, Chen M, and Xu B. Endothelial nitric oxide synthase polymorphisms and erectile dysfunction: A meta-analysis. J Sex Med 2015;12:1319–1328.     

Association between TGF-β1-509C/T polymorphism and endometriosis: a systematic review and meta-analysis

Objective

To evaluate the association between the transforming growth factor β1 gene-509C/T (TGF-β1-509C/T) polymorphism and the risk of endometriosis.

Study design

Relevant studies published before October 2011 were identified by searching PubMed and Embase. Studies were selected using prior defined criteria. The strength of the relationship between the TGF-β1-509C/T polymorphism and endometriosis risk was assessed by Odds Ratios (ORs). Fixed- or random-effects model was calculated according to study heterogeneity. Stratification analysis and sensitivity analysis were also conducted. Possible publication bias was tested by funnel plots and Egger's test.

Results

Of 49 potentially relevant studies, six case–control studies were identified in this meta-analysis. The integrated result showed that the TGF-β1-509C/T polymorphism was not associated with the endometriosis risk for the allele contrast (T vs. C: OR = 1.57, 95%CI = 0.88–2.79), the additive genetic model (T/T vs. C/C: OR = 2.96, 95%CI = 0.97–9.10), the dominant genetic model (T/T + T/C vs. C/C: OR = 1.80, 95%CI = 0.80–4.07) and the recessive genetic model (T/T vs. C/C + T/C: OR = 1.91, 95%CI = 0.89–4.12). In the stratified analysis by ethnicity, genotyping method and source of control, no significantly association was found. Publication bias was not detected in the included studies.

Conclusions

Meta-analyses of the available data showed that the association between TGF-β1-509C/T polymorphism and susceptibility of endometriosis was not significant. More studies are needed to elucidate its role in endometriosis.     

Maternal and fetal HLA-G 14 bp gene polymorphism in pregnancy-induced hypertension,preeclampsia, intrauterine growth restricted and normal pregnancies

Objective: Trophoblast expression of Human Leukocyte Antigene-G (HLA-G) is essential for feto-maternal immune tolerance and successful placentation. There is contradicting evidence on the relationship between HLA-G polymorphisms and preeclampsia (PE), intrauterine growth restriction (IUGR) and pregnancy-induced hypertension (PIH). Here, we investigate the association between both maternal and fetal HLA-G 14?bp insertion/deletion polymorphism and obstetrical complications.

Methods: Clinical and genetic data of 282 women/fetuses (31 severe PE, 8 mild PE, 46 IUGR, 42 PIH and 155 controls) were analyzed both individually and jointly under a codominant, a dominant and a recessive model.

Results: HLA-G 14?bp polymorphism was not associated with obstetrical complications, considering the mother and fetus genotypes both jointly and individually.

Conclusions: With this study we filled several gaps occurring in previous studies: we analyzed a very well-defined population of PE, PIH and IUGR pregnancies, considering both fetal and maternal HLA-G 14?bp polymorphism, individually and jointly. Our findings showed that fetal and maternal HLA-G 14?bp genotypes are not associated with increased risk for the development of obstetrical complications, suggesting that this polymorphism has no immuno-modulatory role in the development of PE, PIH or IUGR.     

Polymorphisms of the methylenetetrahydrofolate reductase gene (C677T and A1298C) in nulliparous women complicated with preeclampsia

Objective: To determine the prevalence of C677T and A1298C Single-nucleotide polymorphisms (SNPs) of the MTHFR gene in nulliparous women complicated with preeclampsia (PE).

Methods: One hundred fifty gestations complicated with PE and their corresponding controls without the disease were recruited for the genotyping of C677T and A1298C polymorphisms of the MTHFR gene using restriction fragment length polymorphism polymerase chain reaction. Secondarily, homocysteine (HCy) plasma levels were measured in preeclamptic women displaying the CC genotype of the A1298C polymorphism (homozygous) and compared to HCy levels determined among controls with the normal AA genotype for the A1298C variant.

Results: Only the mutant CC genotype of the A1298C polymorphism was associated to higher risk of presenting PE, as frequency of this genotype was significantly higher among cases than controls (15.3% versus 0.7%, p?p?=?0.0001). Women with the mutant CC A1298C SNP displayed higher plasma HCy levels as compared to controls with normal AA A1298C genotype (8.4?±?2.6 versus 7.5?±?2.7?mmoL/L p?=?0.04).

Conclusion: Prevalence of the CC mutant genotype of the A1298C polymorphism was higher among PE women. This mutation among PE women was related to increased neck circumference and higher HCy levels. Future research should aim at linking these gestational findings with obesity and cardiovascular risk.     

Genetic susceptibility analysis of GCLC rs17883901 polymorphism to preeclampsia in Chinese Han women

Abstract

Preeclampsia (PE) is a specific obstetric disorder that may result in maternal and neonatal morbidity and mortality. Increasing evidence has been indicated that some candidate genes related to oxidative stress, such as glutamate-cysteine ligase, catalytic subunit (GCLC), glutamate-cysteine ligase, modifier subunit (GCLM), involve in the pathogenesis of PE. After the genetic contribution of GCLC rs17883901 polymorphism was analyzed by TaqMan allelic discrimination real-time PCR in 1001 PE patients and 1182 normal pregnant women, a case-control association analysis was performed. Although no statistical difference was found in genetic distribution of rs17883901 in GCLC between PE and control group (χ²?=?2.201, p?=?.333 by genotypic, χ²?=?0.524, p?=?.469, OR?=?0.932, 95%CI?=?0.771–1.128 by allelic), significant differences in the genotypic frequencies were investigated between mild PE group (χ²?=?6.999, p?=?.030) or late-onset PE group (χ²?=?6.197, p?=?.045) and control group. Furthermore, when dividing the mild PE patients, the late-onset PE patients and the controls into TT/CT?+?CC, TT?+?CT/CC, and TT/CC subgroups, we found statistical differences between mild PE and controls (TT/CT?+?CC:χ²?=?5.132, p?=?.023, OR?=?2.948, 95%CI?=?1.107–7.854; TT/CC:χ²?=?4.564, p?=?.033, OR?=?2.793, 95%CI?=?1.046–7.460) as well as late-onset PE and controls (TT/CT?+?CC:χ²?=?4.043, p?=?.044, OR?=?2.248, 95%CI?=?1.000–5.055). This is the first study to indicate GCLC rs17883901 polymorphism may be associated with a risk of mild PE and late-onset PE in Chinese Han women. However, additional well-designed studies with multi-ethnic and large-scale samples should be performed to validate our results.